Download Graft-Versus-Host Disease

Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
November 2006
Graft-Versus-Host Disease
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, M.D.
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
History
21-year-old male presents with 2 days of
nausea, vomiting, diarrhea
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Supine
Our Patient’s Abdominal
Plain Films
PACS, BIDMC
Upright
PACS, BIDMC
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Our Patient
Axial CT Slice
Target sign
Increased
mesenteric
fat
Featureless
small bowel
PACS, BIDMC
Non-contrast coronal CT
PACS, BIDMC
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Findings on CT
Featureless small bowel
Mild bowel wall thickening
Increased visceral fat
“Target” pattern of bowel
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
History
21-year-old male presents with 2 days of
nausea, vomiting, diarrhea
Day 39 s/p allogenic bone marrow
transplant for non-Hodgkin lymphoma
Acute graft-versus-host-disease
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
GVHD Overview
Complication of allogenic bone marrow
transplantation in which mature donor
lymphocytes attack recipient tissues (including
intestinal mucosa)
T-cells present in the graft produce inflammatory
cytokines, including TNF-α and IL-1
HLA antigens principal initiators GVHD
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Borrowed from Dr. Hines-Peralta
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Epidemiology
Occurs in up to 50 % of patients who
receive an allogenic transplant from an
HLA-identical sibling
Risk factors
– HLA disparity
– Older age
– Donor and recipient gender disparity
– Splenectomy
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Acute vs Chronic GVHD
Acute GVHD
Chronic GVHD
Time of onset
≤ 100 d posttransplant
> 100 d posttransplant
Target tissues
liver, skin, and GI
tract
Clinical
manifestation
Liver, skin, GI – oral
mucosa and
esophagus
Rash, skin blistering, Rash, dry/irritated
diarrhea, abdominal eyes, pain/dryness
in mouth, dysphagia
pain, nausea and
from esophageal
vomiting
involvement
Now, let’s focus on the radiological
manifestations of GVHD
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Intraluminal
Hemorrhage
GVHD –
Companion
Patient #1
Contrast study of the GI tract
Coy et al, Radiolographics 2003
Contrast-enhanced axial CT
Featureless
small bowel
Courtesy of J. Kruskal
Now, back to our patient…
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
GVHD – Our Patient
Target sign
Increased
mesenteric
fat
Featureless
small bowel
PACS, BIDMC
Axial CT Slice
Non-contrast coronal CT
PACS, BIDMC
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Radiologic Findings
Diffuse featureless loops of bowel with
loss of mucosal pattern
Submucosal
edema
“Target” sign
or “halo” sign
http://faculty.southwest.tn.edu/jiwilliams/models_of_the_digestive_system.htm
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Differential Diagnosis of GVHD
Neutropenic Colitis (Typhlitis)
Pseudomembranous Colitis
Infectious Colitis
Inflammatory Bowel Disease
Jaime Wilson-Chiru, HMS III
GVHD
Gillian Lieberman, MD
Companion Patient #2:
Neutropenic Colitis
Coy et al, Radiolographics 2003
Wall
thickening
Diffuse wall
thickening
Fat stranding
Fat
Stranding
Mucosal pattern
remains
Contrast-enhanced axial CT
Kirkpatrick et al, Radiology 2003
Jaime Wilson-Chiru, HMS III
GVHD
Gillian Lieberman, MD
Companion Patient #3:
C. diff. Colitis
Mucosal
irregularity
Wall
thickening
Coy et al, Radiolographics 2003
Diffuse wall
thickening
Mucosal
irregularity
Contrast-enhanced axial CT
Coy et al, Radiolographics 2003
Shaggy wall
contour
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Diagnosis of GVHD
Diagnosis from clinical grounds, with
radiological and histological confirmation
Severity of disease is variable
Grading determined by an assessment of
the degree of involvement of the skin,
liver, and GI tract
Stage of Acute GVHD by Organ System
ORGAN
GRADE
DESCRIPTION
Skin
+1
Maculopapular rash over <25 % of body area
+2
Maculopapular rash over 25 to 50 % of body area
+3
Generalized erythema
+4
Generalized erythema with bullous formation, desquamation
+1
Bilirubin 2.0 to 3.0 mg/dL; SGOT 150 to 750
+2
Bilirubin 3.1 to 6.0 mg/dL
+3
Bilirubin 6.1 to 15.0 mg/dL
+4
Bilirubin >15.0 mg/dL
+1
Diarrhea >30 mL/kg or >500 mL/day
+2
Diarrhea >60 mL/kg or >1000 mL/day
+3
Diarrhea >90 mL/kg or >1500 mL/day
+4
Diarrhea >90 mL/kg or abdominal pain with or without ileus
>2000 mL/day
Liver
Gut
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Prophylaxis & Treatment
Prophylactic regimen a combination of
methotrexate and cyclosporine
Corticosteroids first and most effective
treatment option
One study demonstrated a 30% cure rate
of moderate to severe acute GVHD
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Conclusions
Patients who undergo hematopoietic cell
transplant are at risk for GVHD
Radiological manifestations of GVHD can
look like other inflammatory and infectious
entities
Prompt diagnosis is essential, since
prognosis is dependent on early treatment
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
Acknowledgements
Andrew Hines-Peralta, MD
Gillian Lieberman, MD
Pamela Lepkowski
Larry Barbaras, Webmaster
Jaime Wilson-Chiru, HMS III
Gillian Lieberman, MD
References
1. Chao, NJ. Pathogenesis of graft-versus-host-disease. UpToDate.
http://www.uptodate.com. Accessed 11/08/2006.
2. Coy, DL, et al. Imaging Evaluation of Pulmonary and Abdominal
Complications Following Hematopoietic Stem Cell Transplantation.
Radiographics 2005; 25:305-318.
3. Gore, RM, et al. Inflammatory Conditions of the Colon. Seminars in
Roentgenology 2001; 2:126-137.
4. Iwasaki, T. Recent Advances in the Treatment of Graft-Versus-Host
Disease. Clinical Medicine and Research 2004; 2(4):243-252